Introduction: The NIAS Concept and the Regulatory Context
Ensuring the chemical safety of packaging materials that come into contact with food is not limited to monitoring substances that are intentionally added during the manufacturing process (Intentionally Added Substances—IAS). Article 3 of the European Union’s Framework Regulation (EC) No. 1935/2004 and Regulation (EU) No. 10/2011 on plastic materials require manufacturers to identify unintentionally added substances (NIAS) and conduct a risk assessment. NIAS can originate from impurities in raw materials, by-products of reactions occurring during production, degradation products, or environmental contaminants. With the introduction of the PPWR, this obligation has become even clearer, requiring packaging manufacturers to approach NIAS assessment with a systematic approach. Nano-Test Labor Services offers a comprehensive and GLP-compliant portfolio of services in the field of NIAS assessment, ranging from screening and identification tests using advanced analytical techniques to toxicological risk assessment.
Definition, Sources, and Classification of NIAS
NIAS is a broad term that encompasses all chemical substances that were not intentionally added to the formulation of a packaging material but may be present in the final product. The sources of these substances are diverse and can arise throughout the entire life cycle of the packaging. A proper understanding of NIAS is crucial for developing an effective analytical strategy and conducting a risk assessment.
Classification of NIAS Sources
The following table systematically summarizes the main formation mechanisms, sources, and typical examples for each source:
| NIAS Source | Mechanism of Formation | Typical NIAS Examples |
|---|---|---|
| Impurities in the raw materials | Residues from the monomer manufacturing process, additives, or solvent residues originating from the production process | Monomer isomers, solvent residues, catalyst residues, impurities in technical-grade chemicals |
| Reaction byproducts | Undesirable compounds formed during polymerization, cross-linking, or curing reactions | Oligomers (dimers, trimers), polymerization byproducts, decomposition products |
| Degradation products | Thermal, photochemical, or hydrolytic degradation of the polymer or additives | Decomposition products of antioxidants, decomposition products of UV stabilizers, depolymerization oligomers |
| Verunreinigungen aus dem Recycling</ strong> | Foreign substances that enter the recycled raw material, or residues from its previous use | Printing ink components, adhesive residues, residues from previous products, MOSH/MOAH |
| Environmental contaminants | Substances that originate from the environment during manufacturing, storage, or transport | PAHs (polycyclic aromatic hydrocarbons), PCBs, pesticide residues |
Note: The scope of the NIAS assessment is determined on a case-by-case basis, taking into account the composition of the packaging material, the manufacturing process, and the intended conditions of use. The guidance documents published by EFSA provide the basic methodological framework for the NIAS assessment.
Analytical Strategy for the NIAS Assessment
NIAS assessment is one of the most complex areas of analytical chemistry due to the need to simultaneously screen and identify a large number of known and unknown substances. At the Nano-Test Laboratory, NIAS assessment is conducted using the following multi-step, systematic approach.
Step-by-Step NIAS Assessment Strategy
The NIAS evaluation process used by Nano-Test consists of four main phases, which are summarized in the following table:
| Phase | Step | Explanation |
|---|---|---|
| 1. Preliminary Assessment and Data Collection | Review of information regarding the formulation and manufacturing process | Theoretical identification of all raw materials, additives, production parameters, and potential sources of NIAS (impurities, reaction byproducts, decomposition products) used. During this phase, the supplier declarations and safety data sheets (SDS) provided by the customer are also evaluated. |
| 2. Non-Targeted Screening | Comprehensive screening using high-resolution mass spectrometry (HRMS) | The extract obtained following an appropriate extraction and/or migration test is analyzed using LC-QTOF-MS and GC-QTOF-MS systems. The data obtained are evaluated using advanced data processing software to perform a library search and identify unknown peaks. |
| 3. Identification and semiquantitative determination | Structural characterization of the identified NIAS candidates | The structural characterization of unknown compounds is based on the exact mass, isotopic distribution, and MS/MS fragmentation patterns obtained from the HRMS data. Where possible, validation is performed using reference standards. Semiquantitative estimation is performed using an approach based on internal standards or structural analogs. |
| 4. Toxicological Risk Assessment | Assessment of the identified NIAS with regard to food safety | For each identified NIAS, a risk assessment is conducted using EFSA’s “Threshold of Toxicological Concern” (TTC) approach or substance-specific toxicological data. The Cramer classification and genotoxicity warnings (QSAR) are taken into account. |
Nano-Test NIAS Analysis Platforms
The main analytical platforms used in the Nano-Test laboratory for NIAS evaluation, along with their specific roles in NIAS analysis, are compared in the following table:
| Analytical Platform | Technical Specifications | Role in the NIAS analysis | Target Composite Profile |
|---|---|---|---|
| LC-QTOF-MS | High resolution (≥30,000 FWHM), high mass accuracy (±3 ppm), MS/MS fragmentation | Target-free screening and identification of polar and moderately polar NIAS | Oligomers, degradation products, antioxidants and their metabolites, plasticizers, lubricants |
| GC-QTOF-MS | High resolution, EI and CI ionization, extensive library (NIST, Wiley) | Targets: Unbiased screening and identification of volatile and semi-volatile NIAS | Volatile organic compounds (VOCs), low-molecular-weight oligomers, solvent residues |
| LC-MS/MS (QQQ) | Triple quadrupole, MRM mode, high selectivity and sensitivity | Targeted quantitative determination and validation of identified NIAS | Specific NIAS compounds (BPA, phthalates, PAA, etc.) |
| Headspace-GC-MS | Headspace sampling, optimized for volatile compounds | Screening and Quantification of Volatile NIAS | Residual monomers (styrene, butadiene), solvents, volatile degradation products |
Toxicological Risk Assessment and the TTC Approach
The ultimate goal of the NIAS assessment is to determine whether the identified substances pose a risk to consumer health. The “Threshold of Toxicological Concern” (TTC) approach adopted by EFSA provides a scientifically sound tool for risk assessment of substances whose structure is known but for which only limited toxicological data are available.
During this crucial phase of the NIAS evaluation, Nano-Test applies the following systematic approach:
Cramer Classification and TTC Thresholds
The following table summarizes the toxicological potential of the substances according to the Cramer classification system and the corresponding TTC thresholds:
| Cramer Class | Toxicity potential | TTC threshold (μg/kg body weight/day) | Typical Chemical Structures |
|---|---|---|---|
| Class I | Low toxicity potential | 30 | Simple aliphatic hydrocarbons, normal metabolic products |
| Klasse II</ strong> | Moderate toxicity potential | 9 | Compounds containing functional groups without aromatic rings, esters, ethers |
| Class III | High Toxicity Potential | 1, 5 | Aromatic compounds, heterocyclic structures, conjugated systems |
| Genotoxic Substances | Suspected DNA-reactive genotoxicity | 0.0025 (for a lifetime cancer risk of 1 in 10⁵) | Aflatoxin-like structures, N-nitroso compounds, DNA intercalators |
Note: The EFSA does not recommend applying the TTC approach to genotoxic carcinogens. For such substances, minimizing exposure (the ALARA principle) is of fundamental importance. Furthermore, the TTC approach may not be suitable for groups of substances with potentially neurotoxic effects, such as organophosphates and carbamates.
Nano-Test's Integrated NIAS Evaluation Service
At Nano-Test Labor Services, we offer NIAS assessment using a multidisciplinary and integrated approach. Our service model consists of the components summarized in the following table:
The NIAS assessment is not merely an analytical test, but a multifaceted process that requires in-depth chemical and toxicological expertise. At Nano-Test, we approach every stage of this process with a commitment to GLP principles, scientific rigor, and a customer-focused consulting philosophy.The NIAS assessment is not merely an analytical test, but a multifaceted process that requires in-depth chemical and toxicological expertise. At Nano-Test, we operate in accordance with GLP principles, scientific rigor, and a customer-focused consulting approach at every stage of this process.To ensure the NIAS compliance of the packaging you export to the European market under the PPWR and relevant EU regulations, and to conduct your screening and risk assessment processes with a reliable partner, please contact our team of experts to receive detailed information about Nano-Test’s NIAS assessment services.
| Service Component | Scope | Benefits for the Customer |
|---|---|---|
| Formulation and Process Testing | Detailed analysis of the raw materials and additives used, as well as the production process; theoretical mapping of potential NIAS sources | Designing the right analysis strategy, avoiding unnecessary analyses |
| Non-target screening (HRMS) | Comprehensive, non-targeted chemical screening using LC-QTOF-MS and GC-QTOF-MS | Detection of unexpected contaminants and unknown NIAS |
| Structural Illumination and Semi-Quantification | Structural characterization based on HRMS data and semiquantitative estimation using internal standards | Reliable identification of unknown peaks and determination of their approximate concentrations |
| Toxicological Risk Assessment | Comprehensive risk assessment using the TTC approach, the Cramer classification, and QSAR toxicity prediction (in silico) | Scientifically Based Assessment of the Food Safety Risk Posed by the Defined NIAS |
| Regulatory Compliance Report | Comprehensive report for the DoC (Declaration of Conformity) that includes all analytical results and the risk assessment | Complete documentation for regulatory applications and customer audits |
To ensure that your packaging, which you export to the European market, complies with NIAS under the PPWR Regulation and relevant EU legislation, and to implement your targeted testing and risk assessment procedures in collaboration with a reliable partner, you can contact our team of experts to receive detailed information about Nano-Test’s NIAS assessment services.